Project Summary/Abstracts Cervical cancer remains a significant health problem in low- and middle- income countries (LMICs). More than 80% of the 530,000 annual cervical cancer cases and 270,000 annual cervical cancer-related deaths occur in LMICs. Lack of resources for conducting organized screening and treatment services in LMICs leads to late stage diagnosis of cervical malignancy. As a result of this resource shortage, cervical cancer associated mortality rate in east African countries is 27.6 per 100,000, which is unacceptably high when compared to 2.3 per 100,000 in the US. Visual inspection with acetic acid (VIA) and HPV tests are the two low-cost screening approaches commonly utilized in LMICs. Several studies showed that cervical cancer incidence rate can be reduced by screening with HPV and VIA tests and treating the patient accordingly. However, main drawback of the VIA and HPV tests is low specificity, as most women with a positive screening result (80% to 90%) will not have significant cervical malignancy that warrants treatment (i.e., cervical precancer or cancer). The resulting overtreatment exposes low-risk women to unnecessary morbidity and poses a strain on resources. Confocal microscopy provides both high sensitivity (93-100%) and specificity (93-100%) in detecting cervical precancer but its utility in LMICs has been limited due to the high device cost (>$50,000). We are proposing a new approach of accurately diagnosing cervical precancer with a low-cost (<$3,000) smartphone confocal endoscope and providing adequate treatment in a single visit. In this approach, suspected cervical lesions are imaged in vivo with the smartphone confocal endoscope. Cellular morphologies visualized in confocal images are quantitatively analyzed to diagnose cervical precancer and adequate treatment is performed during the same visit. Our approach will improve patient care in two areas: i) with high specificity of confocal microscopy, we will be able to reduce unnecessary overtreatment; and ii) with the low device cost, we will enhance a single- visit, ?screen-and-treat? method in rural clinics. In this R21 project, we will develop the smartphone confocal endoscope and conduct a pilot study of imaging cervix in vivo in Uganda. We have previously developed a low- cost smartphone confocal microscope and have demonstrated in vivo confocal skin imaging in Uganda. In this project, we are translating the smartphone confocal microscopy technology for cervical imaging by developing a miniature endoscopic catheter. In Aim 1, we will develop a smartphone confocal endoscope for imaging cervix. We will optimally design i) a low-cost smartphone confocal module that connects with ii) a miniature endoscopic catheter and test the imaging performance. In Aim 2, we will demonstrate in vivo confocal imaging of cervix in patients in Uganda. Confocal images will be analyzed in comparison with corresponding histologic images and preliminary analysis will be conducted on diagnostic accuracy. We strongly believe that our low- cost, smartphone confocal microscopy technology will greatly improve the early diagnosis of a range of conditions, with the ultimate goal of helping to reduce health disparity around the globe.